denifanstat (TVB-2640) / Sagimet Biosci, Ascletis - LARVOL DELTA

Denifanstat for Moderate-to-Severe Acne Vulgaris: Results from an Open-label, Multicenter, Phase III Extension Study (EADV 2026) - No abstract available

Clinical • P3 data • Acne Vulgaris • Dermatology

Asciminib (ASC) in Combination with Imatinib (IMA), Nilotinib (NIL), or Dasatinib (DAS) May be a Potential Treatment (Tx) Option in Patients (Pts) with Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase or Accelerated Phase (Ph+ CML-CP/AP): Final Results from the Asciminib Phase 1 Study (ASH 2023) - P1 | "INTRODUCTION: ATP-competitive tyrosine kinase inhibitors (TKIs) have extended the life expectancy of pts with CML. ASC in combination with ATP-competitive TKIs, while associated with a higher AE burden vs ASC monotherapy, demonstrated rapid efficacy in the enrolled pt population. The MTD for ASC + IMA was reached at ASC 60 mg QD + IMA 400 mg QD (Table); the MTD for ASC + NIL or DAS was not reached. ASC 40 or 60 mg QD + IMA 400 mg QD, ASC 40 mg BID + NIL 300 mg BID, and ASC 80 mg QD + DAS 100 mg QD were recommended doses for expansion."

Clinical • Combination therapy • P1 data • Chronic Myeloid Leukemia • Fatigue • Hematological Malignancies • Leukemia • Oncology

Sustained Efficacy and Safety with Asciminib (ASC) after Almost 4 Years of Median Follow-up from Ascembl, a Phase 3 Study of ASC Vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Prior Tyrosine Kinase Inhibitors (TKIs): An End of Study Treatment (EOS Tx) Update, Including Results from Switch Population (ASH 2023) - " Adults (aged ≥18 y) with CML-CP after ≥2 prior TKIs, with intolerance or lack of efficacy per 2013 ELN recommendations were randomized 2:1 to receive either ASC 40 mg twice daily or BOS 500 mg once daily. With almost 4 y of follow-up in ASCEMBL, ASC continued to show greater efficacy and better safety/tolerability than BOS in pts with CML-CP after ≥2 prior TKIs. The robust safety profile of ASC was sustained through each analysis in ASCEMBL (wk 24, wk 96, and EOS Tx), confirming that pts receiving ASC can maintain a high level of response and continue Tx without experiencing late-emerging AEs. Results in the switch population support the use of ASC early in the Tx paradigm."

Clinical • P3 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

Fatty acid synthase in cardiovascular disease: from molecular mechanisms to therapeutic targeting. (PubMed, Cardiovasc Res) - "Pharmacological FAS inhibitors, including TVB-2640 (denifanstat), demonstrate acceptable safety profiles in clinical trials and reduce hepatic de novo lipogenesis by 50-70%, while platensimycin reduces atherosclerotic burden in preclinical models. These findings position FAS as both a mechanistic driver and promising therapeutic target for cardiovascular disease. However, the divergent consequences of FAS modulation across tissues underscore the need for targeted delivery strategies that suppress pathological lipogenesis while preserving essential cardiac functions."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • Peripheral Arterial Disease • FASN

A new era in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD): clinical breakthroughs and challenges. (PubMed, Front Pharmacol) - "Metabolic dysfunction-associated steatotic liver disease (MASLD), affecting nearly one-third of adults worldwide, encompasses a spectrum from steatosis to steatohepatitis (MASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma, with fibrosis stage as the primary determinant of liver-related outcomes and cardiovascular disease as the leading cause of mortality. The period 2024-2026 has marked a transformative shift, with resmetirom (thyroid hormone receptor-β agonist) gaining accelerated approval in 2024 as the first agent to meet histologic endpoints in MASH, followed by semaglutide (GLP-1 receptor agonist) in 2025, both demonstrating substantial MASH resolution and fibrosis improvement in phase 3 trials; a diverse pipeline, including tirzepatide, efruxifermin, lanifibranor, denifanstat, and dual-incretin agonists, has yielded promising histologic and metabolic outcomes, with several advancing to phase 3 and updated guidelines endorsing pharmacotherapy for..."

Journal • Cardiovascular • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor

Asciminib (ASC) Add-on to Imatinib (IMA) Demonstrates Sustained High Rates of Ongoing Therapy and Deep Molecular Responses (DMRs) with Prolonged Follow-up in the ASC4MORE Study (ASH 2023) - P2 | "Here, we report results of ASC add-on to IMA vs continued IMA vs switch to nilotinib (NIL) and of pts who crossed over from continued IMA to ASC add-on after 96 wks of Tx in pts not achieving DMR with ≥1 y of IMA as their first TKI (cutoff: 6 Mar 2023)...The top reasons for discontinuation were pt decision (9.5% with ASC 40 mg add-on), adverse events (AEs; 14.3% and 33.3%, with ASC 60 mg add-on and NIL, respectively), and physician decision (66.7% with IMA, all of whom crossed over to ASC 60 mg add-on)... Among pts not achieving DMR after ≥1 y on IMA, more pts achieved MR4.5 with ASC add-on to IMA than with continuing IMA or switching to NIL at wk 96. Pts crossing over from IMA to ASC 60 mg add-on were still able to achieve DMRs. ASC add-on to IMA was well-tolerated, with no new or worsening safety findings compared with those known for ASC alone."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Integrating proteomics and metabolomics to reveal MAT2A for metabolic reprogramming in non-small cell lung cancer cells. (PubMed, iScience) - "In fatty acid biosynthesis, MAT2A regulates FASN and SCD; exogenous palmitic acid reverses AG-270-induced growth inhibition, supporting combination with the FASN inhibitor TVB-2640. In the transsulfuration pathway, MAT2A transcriptionally regulates CBS and shows synergy with inhibitors of PHGDH (producing serine for cysteine biosynthesis) and SLC7A11 (mediating cysteine uptake). Collectively, our findings establish MAT2A as a central metabolic regulator in NSCLC and propose rational combination strategies."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HIF1A • MAT2A • PHGDH • SLC2A1 • SLC7A11

Efficacy and Safety Results from ASC4MORE, a Randomized Study of Asciminib (ASC) Add-on to Imatinib (IMA), Continued IMA, or Switch to Nilotinib (NIL) in Patients (Pts) with Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Not Achieving Deep Molecular Responses (DMRs) with ≥1 Year of IMA (ASH 2022) - P2, P3 | "In the phase 3 ASCEMBL study, ASC led to superior major molecular response vs bosutinib (BOS) at wk 24 and 96...Top reasons for discontinuation were pt decision in the ASC 40-mg add-on arm (9.5%), AEs in the ASC 60-mg add-on and NIL arms (14.3% and 23.8%, respectively), and physician decision in the IMA arm (57.1%) (pts who crossed over to the ASC 60-mg add-on arm were considered discontinued for IMA arm)... More pts achieved DMR at wk 48 with ASC add-on to IMA vs continued IMA or switch to NIL in pts not achieving DMR with IMA alone for ≥1 y. In this population of pts tolerating IMA for ≥1 y, ASC add-on was generally well tolerated. While not powered to identify the best arm for achievement of DMR in this setting, the high rate of DMR in the ASC add-on arms is promising. Further studies are needed to assess if ASC alone can provide equivalent efficacy and better tolerability vs add-on to IMA."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Impact of Mutations in Blood Cancer–Related Genes on Clinical Outcomes in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Tyrosine Kinase Inhibitors (TKIs) in the Ascembl Trial (ASH 2023) - "With >2 years of follow-up in the phase 3 ASCEMBL study, asciminib (ASC) has continued to demonstrate superior efficacy vs bosutinib (BOS) in pts with CML-CP after ≥2 prior TKIs, and analysis of cancer gene somatic mutations in this population has the potential to reveal additional insights into pts' response to study treatments or characteristics of the disease in later lines of therapy... Adults with CML-CP previously treated with ≥2 TKIs with intolerance of their last TKI or lack of efficacy per 2013 European LeukemiaNet recommendations and without BCR::ABL1 T315I or V299L mutations were randomized 2:1 to ASC 40 mg twice daily or BOS 500 mg once daily... ASXL1 mutations are most frequently detected at CML diagnosis and were enriched at BL in this study of pts with CML-CP previously treated with ≥2 TKIs, which is consistent with a role in TKI resistance. RUNX1 and IKZF1 mutations, which are associated with progression to accelerated or blast phase in CML, were..."

Clinical • Clinical data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ASXL1 • IKZF1 • RUNX1

A phase 2 multi-center pharmacodynamic study of the fatty acid synthase (FASN) inhibitor TVB-2640 in advanced KRAS-mutant non–small cell lung cancer. (ASCO 2026) - P2 | "Single-agent FASN inhibition with TVB-2640 in heavily pretreated KRAS mutant NSCLC did not meet the primary endpoint of response. Since FASN is a downstream effector of mutant KRAS, combination regimens with KRAS inhibitors can be considered as a future approach in NSCLC. Ongoing correlative studies may further inform the use of this agent."

Clinical • IO biomarker • Metastases • P2 data • PK/PD data • Dental Disorders • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Xerostomia • FASN • KRAS

Designing a novel 3D co-culture model incorporating patient T-cells to study lipid metabolism as a metabolic vulnerability in KRAS driven non-small cell lung cancer (AACR 2026) - P | "Fatty acid synthase (FASN) inhibitor, TVB-2640, showed the greatest efficacy in KL cells...Moreover, we have developed a novel 3D co-culture model using NSCLC cells and patient T-cells. Further analysis, supported by our 3D co-culture model, aims to analyse the consequences of targeting fatty acid synthesis in combination with immunotherapy in the KL genotype of NSCLC."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CASP3 • IL2 • KL • KRAS • STK11 • TP53

Sagimet Biosciences…announced that its AURORA Phase 3 clinical trial of FASN inhibitor denifanstat in moderate to severe acne is on track to initiate enrollment in Q4 2026 (GlobeNewswire) - "The AURORA multi-center, randomized, double-blind, placebo-controlled Phase 3 clinical trial of denifanstat in moderate to severe acne is intended to enroll approximately 800 U.S. patients aged 12 years and older, of which 450 are expected to be adolescents aged 12 to 17 years....Patient screening expected to begin in October 2026, with first patient to be enrolled shortly after."

New P3 trial • Acne Vulgaris

Productive Mayaro Virus Infection Requires Host Fatty Acid Synthase for nsP1 S-palmitoylation. (PubMed, bioRxiv) - "In addition, we report that inhibiting FASN with the clinically advanced small molecule TVB-2640 significantly reduced MAYV infection and nsP1 palmitoylation. This study highlights FASN as an essential host factor for MAYV replication and establishes it as a promising therapeutic target for MAYV and related alphaviruses."

Journal • Chikungunya • Infectious Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • ALK • FASN

TVB-2640 and Trastuzumab With Paclitaxel or Endocrine Therapy for Treatment of HER2 Positive Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=17 | Completed | Sponsor: Mayo Clinic | Active, not recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Mar 2026

Trial completion • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Denifanstat in acne therapy: A promising step forward. (PubMed, J Eur Acad Dermatol Venereol) - No abstract available

Journal • Acne Vulgaris

Investigating the Role of Fatty Acid Synthase Inhibition on Immune Checkpoint Expression in Prostate Cancer (EACR 2026) - "The current results show that both orlistat and denifanstat have anti-cancer effects and we are currently investigating how this relates to PD-L1 expression."

IO biomarker • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • FASN

ASCIMINIB IN CHRONIC-PHASE CML AFTER PRIOR TKI INTOLERANCE OR RESISTANCE: REAL-WORLD OUTCOMES FROM A SINGLE-CENTER COHORT (EHA 2026) - "Twelve patients (80 %) had previously received imatinib, 6 (40 %) dasatinib, 6 (40%) nilotinib, 1(6.7%) bosutinib, and 2 (13.3%) ponatinib...Initially, 7 (46.6%) patients received ASC 40 mg BID, 7 (46.6%) 80 mg QD, and 1 (7%) 200 mg BID due to T315I mutation...Summary/Conclusion ASC showed favorable tolerability and meaningful molecular responses in this heavily pretreated CP-CML cohort with significant comorbidities. Discontinuation due to newly emergent or recurring toxicity was at low rates, supporting ASC as an effective and safe option in patients requiring therapy change due to standard TKI intolerance or resistance."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Hypertension • Leukemia • Musculoskeletal Pain

Transcriptomic analysis revealed distinct mechanisms underlying the synergistic effect of a fatty acid synthase inhibitor and resmetirom combination in LDL receptor knockout MASH mice (EASL 2026) - " Male Ldlr-/- mice were fed a fast-food diet (FFD) for 18 weeks to induce MASH features and treated with TVB-3664 (a FASN inhibitor surrogate for denifanstat, 5 mg/kg, PO, QD) or Res (MGL-3196, 3 mg/kg, PO, QD) alone or in combination for 10 weeks. Transcriptomic analysis confirmed that combination of a FASN inhibitor and resmetirom increased the anti-inflammatory and anti-fibrotic effects, and enhanced metabolic correction associated with lipid and cholesterol synthesis in a mouse model of MASH and dyslipidemia. These findings support future clinical evaluation of this combination therapy in MASH."

Omic analysis • Preclinical • Dyslipidemia • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • COL1A1 • FASN • TGFB1

Sagimet Biosciences Presents…Posters at EASL 2026 on Denifanstat/Resmetirom Combination in MASH (GlobeNewswire) - "The Phase 1 open label clinical trial evaluated the safety, pharmacodynamics, and pharmacokinetics of the denifanstat/resmetirom combination in 40 healthy adults with a mean BMI of 30-32 kg/m2....Clinical data reported for the first time at EASL 2026 show rapid reduction in total and LDL cholesterol levels (p<0.001) after two weeks of treatment, suggesting a potential cardiovascular benefit: Cohort 1 (denifanstat followed by denifanstat/resmetirom): total cholesterol -23mg/dl, LDL cholesterol -17mg/dl; Cohort 2 (resmetirom followed by denifanstat/resmetirom): total cholesterol -16mg/dl, LDL cholesterol -14mg/dl."

P1 data • Metabolic Dysfunction-Associated Steatohepatitis

Denifanstat and resmetirom combination therapy rapidly decreased atherogenic lipids in healthy adults in Phase 1 open-label trial (EASL 2026) - "These Phase 1 results showed strong target engagement for Deni and Res, alone and in combination. The combination significantly reduced atherogenic lipids, suggesting cardiovascular benefits. Together with prior fibrosis improvement data, the safety, PD/biomarker and PK results support further clinical evaluation of Deni/Res combination for MASH and fibrosis."

Clinical • Combination therapy • Late-breaking abstract • P1 data • Cardiovascular • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Efficacy of pharmacotherapies in improving liver fibrosis among patients with MASLD and fibrosis stages of F1-F3: systematic review and network meta-analysis. (PubMed, J Transl Med) - "This study supported the use of survodutide (4.8 mg/week), efruxiferimin (28 mg/week), resmetirom (80 mg/day), and denifanstat (50 mg/day) as an recommended regimen in adults with MASLD and fibrosis stages of F1-F3. However, these findings did not support the clinical use of emricasan because of its poor efficacy. Concurrently, multiple pharmacological agents also exhibited efficacy at other relevant clinical endpoints."

Journal • Retrospective data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Poster Title: Transcriptomic analysis revealed distinct mechanisms underlying the synergistic effect of a fatty acid synthase (FASN) inhibitor and resmetirom combination in LDL receptor knockout MASH mice (GlobeNewswire) - "Sagimet Biosciences...announced the presentation of...posters at the European Association for the Study of the Liver (EASL) Annual Congress 2026....The combination of a FASN inhibitor and resmetirom showed greater improvements in liver histology and lipid lowering compared to monotherapy in mouse model of diet-induced MASH. Transcriptomic analysis further characterized the molecular mechanisms driving these effects, showing enhanced anti-inflammatory and anti-fibrotic activity and improved metabolic regulation including lipid and cholesterol synthesis."

Preclinical • Metabolic Dysfunction-Associated Steatohepatitis

Denifanstat: Expiry of patents related to composition-of-matter in 2032 with term extension until 2037 (Sagimet Biosciences) - Corporate Presentation

Patent • Acne Vulgaris • Brain Cancer • CNS Tumor • Dermatology • Glioblastoma • Glioma • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor

Sagimet Biosciences Reports First Quarter 2026 Financial Results and Provides Corporate Updates (Yahoo Finance) - "The company recently completed an underwritten offering...resulting in $175.0 million gross proceeds...existing cash and cash equivalents, together with the proceeds from the offering, will fund its acne programs through 2028 and the data readout of the Company’s planned denifanstat Phase 3 clinical trial in moderate to severe acne."

Commercial • New P3 trial • Acne Vulgaris

Fatty acid synthase (FASN) inhibitors decreased sebum lipids in human sebocytes via inhibition of de novo lipogenesis (DNL), supporting FASN as a target for acne treatment (SID 2026) - "Human sebocytes (SZ95) were treated with FASNi (TVB-3567 and TVB-3664) and acetyl-coA carboxylase inhibitor (ACCi) for 48h +/- insulin and the cellular lipids were used for lipidomic analysis. Preclinical data demonstrated that FASN inhibitors effectively reduced sebum-related lipids in human sebocytes. Following the clinical success of denifanstat in acne, these results provide a strong rationale for the clinical evaluation of FASN inhibitors for acne treatment."

Late-breaking abstract • Acne Vulgaris • FASN